Introduction

Endoscopic submucosal dissection (ESD) has evolved to become a viable treatment option for oesophageal squamous dysplasia (SD) and early squamous cell carcinoma (ESCC). Although enbloc, R0, excision has the potential to yield an endoscopic cure, surgery remains the standard of care in the West. Furthermore, Western data pertaining to endoscopic outcomes is limited. We aimed to assess the efficacy and safety of ESD for SD and ESCC in a single tertiary referral centre.

Aims & Methods

We conducted a prospective observational cohort study over 87 months until November 2023 in consecutive patients undergoing ESD for SD or ESCC. The primary outcomes were enbloc, R0 and curative resection rates. Secondary outcomes included procedure duration, tumor recurrence and adverse events.

Results

112 consecutive patients were referred for treatment and underwent ESD (median age 73 [IQR 68-78]; 50% male; Table 1). Median lesion size was 30 mm (IQR 20-50mm) and Paris IIa was the most common morphology (58.9%). Enbloc resection was achieved in 109 (97.3%) and R0 excision in 87 (77.7%). Curative resection in cases of LGD and HGD, where margins were clear of dysplasia, was 7/11 (63.6%) and 31/34 (91.2%) respectively. In those with T1a/T1b SCC, the curative resection rate was 20/61 (32.8%). In T1a SCC lesions, 11/20 (55.0%) had a curative ESD. Of the remainder, 6/9 were poorly differentiated, 1/9 had LVI, and 2/9 had positive margins (1 deep, 1 peripheral). In T1b SCC lesions, 9/41 were curative (22.0%). The remainder were either poorly differentiated, >T1b-SM1, LVI positive or a combination. In those with T1a/T1b disease, without adverse tumor biology, ESD achieved curative resection in 20/22 (90.9%).
In the 41/61 (67.2%) T1a/T1b patients that did not meet criteria for cure, subsequent treatment included surgery (n=5), radiotherapy (n=5) and chemoradiotherapy (n=1). After MDT discussion, the remaining 30 were managed conservatively, due to advanced age or comorbidities. In these, recurrence occurred in 6/30 patients (1 local, 3 nodal, 2 metastatic) at a median follow up of 12 months (6-18 months). The median hospital length of stay was 1 day (IQR 1-3). Oesophageal strictures occurred in 46 patients (41.1%), requiring a median of 3 dilations (IQR 1-8). There were 2 cases of delayed bleeding. There were no perforations.

Table 1

Conclusion

ESD is curative for low and high-grade dysplasia. In a Western setting, ESD offers definitive T-staging and has the potential to yield a cure in almost 33% of T1a and T1b SCC cases. Due to a high risk of disease recurrence, adjuvant therapy should be considered in cases of a non-curative resection.

Introduction

Etrasimod is an investigational, once-daily (QD), oral, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator in development to treat immune-mediated inflammatory disorders. CULTIVATE (NCT04173273) is a seamless phase 2/3 trial comprising 5 substudies designed to evaluate the efficacy, safety and tolerability of etrasimod in patients with moderately to severely active Crohn’s disease (CD).

Aims & Methods

Here, we report the induction data from the first substudy (Substudy A). Substudy A was a phase 2, randomised, double-blind study using a 14‑week induction period followed by a 52-week extension period. Adults (18–80 years) with moderately to severely active CD and an inadequate response, loss of response or intolerance to ≥1 conventional or advanced treatments for CD were randomised 1:1 to etrasimod 2 or 3 mg QD. Patients were stratified by baseline biologic failure status and oral corticosteroid use. The primary efficacy endpoint was achievement of endoscopic response (defined as endoscopic remission [SES-CD ≤4 and ≥2-point reduction from baseline with no subscore >1] or ≥50% decrease in SES-CD score) at Week 14. Secondary/exploratory endpoints included achievement of endoscopic remission, clinical remission (CDAI <150) and IBDQ remission (IBDQ ≥170), at Week 14. Outcomes were analysed in the full analysis set (all randomised patients treated with ≥1 dose of etrasimod) using non-responder imputation or observed data.

Results

Of 83 patients randomised to either etrasimod 2 or 3 mg QD, 32/42 (76.2%) and 36/41 (87.8%) completed Week 14, respectively. Overall, 21.4% and 9.8% of patients receiving etrasimod 2 and 3 mg QD, respectively, achieved the primary endpoint of endoscopic response, 14.3% and 7.3% achieved endoscopic remission, 31.0% and 43.9% achieved clinical remission, and 33.3% and 40.0% achieved IBDQ remission at Week 14. Most TEAEs were mild or moderate. The incidence of serious TEAEs (4.8% and 2.4%) and TEAEs leading to discontinuation (4.8% and 7.3%) was low with etrasimod 2 and 3 mg QD, respectively (Table). Two patients randomized to etrasimod 3 mg QD experienced second-degree atrioventricular block type I TEAEs (one patient during 2-mg titration).

Conclusion

Data from this substudy of patients with moderately to severely active CD suggest endoscopic and clinical improvement with both etrasimod 2 and 3 mg QD. However, the small sample size and lack of a placebo arm limit the ability to draw conclusions about efficacy, including comparison between the etrasimod 2 and 3 mg groups. Both doses were well tolerated, and safety was consistent with other etrasimod clinical programmes. Data from the extension phase of Substudy A and the placebo-controlled, dose-ranging phase 2b Substudy 1 are forthcoming.

Disclosure

GD’H: advisor: AbbVie, AstraZeneca, Alimentiv, Bristol-Myers Squibb, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson & Johnson, Takeda, Pfizer, Polpharma, Prometheus, Tillotts, Ventyx; speaker: AbbVie, Boehringer Ingelheim, Celltrion, Johnson & Johnson, Takeda, Pfizer, Tillotts.
MCD: grant/research: Janssen; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; shares/royalties: Trellus; directorship/ownership interests: Trellus.
LPB: grant/research: Takeda, Fresenius Kabi, Celltrion; consultancy: AbbVie, Alimentiv, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Bristol-Myers Squibb, Celltrion, CONNECT Biopharm, Cytoki, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer, GSK, HAC, IAG Image Analysis, Index, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM, ONO, OSE, Pandion, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia, Abivax; speaker: Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Eli Lilly, Gilead, Viatris, Medac, Sanofi; stock: CTMA.
SD: consultancy/advisory: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer, Roche, Sandoz, Takeda, TiGenix, UCB, Vifor; speaker: AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda; directorship/ownership interests: Gastroenterology and Endoscopy.
BES: grant/research: Arena, Janssen. Lecture fees/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda; consultancy/advisory: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D; stock: Ventyx Biosciences; non-financial support: Janssen, Lilly, Pfizer, Takeda.
DCW: grant/research: AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer, Takeda, Ventyx; speaker: AbbVie, Bristol Myers, Squibb, Janssen, Pfizer, Takeda; consultancy: AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer, Takeda.
AJY: consultancy: Pfizer, Arena, Takeda, Bristol-Myers Squibb; speaker: Bristol-Myers Squibb.
MVC: grant support: Pfizer, Janssen, Novartis, Bristol-Myers Squibb; consultancy fees: AbbVie, Arena, Bristol-Myers Squibb, Medtronic, Pfizer, Prometheus, Eli Lilly, Janssen, Takeda; speaker fees: AbbVie, Janssen, Medtronic, Pfizer, Bristol-Myers Squibb, Takeda.
DD: employee of Pfizer Inc at the time of the abstract.
IM, HT, GG, CS: employees & shareholders of Pfizer Inc.
CL, FC: employees of Pfizer Inc at the time of this analysis.
JZ: employee & shareholder of Arena Pharmaceuticals.
AMcD: employee & shareholder of Pfizer Ltd.
SS: speaker: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Janssen, MSD, Pfizer, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention, Takeda, Theravance.
BGF: consultant/advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared, Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.
SV: grant/research: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy/advisory: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.

Introduction

Eosinophilic esophagitis (EoE) is a complex disease that often coexists with different conditions. Given the complexity of this pathology, a multidisciplinary approach, with gastroenterologist, allergist, dietitian, psychologist, and endoscopist may benefit to diagnosis and management of patients, reducing time to diagnosis as well.

Aims & Methods

To evaluate impact of multidisciplinary team in diagnosis and management of eosinophilic esophagitis disease. A retrospective study was conducted to include all patients referred to Fondazione Policlinico Universitario A. Gemelli between September 2016 and April 2023. Prevalence of allergic, nutritional, and psychological disturbs was evaluated. Referral for each patient was reviewed. Diagnostic delay (time interval between first occurrence of EoE symptoms and confirmed diagnosis with endoscopy) was analyzed in patients with suspected eosinophilic esophagitis and diagnosis made in our center, compared to data reported in literature. Publications from 2014 to 2023 were reviewed.

Results

A total of 98 patients, 76 males and 22 females, with a mean age at diagnosis of 25 years, were included in the study. For all patients, each visit was conducted in team with gastroenterologist, allergist, dietitian, and psychologist. 81 patients presented allergic diseases (82 %), 51 patients (52 %) needed nutritional support by a dietitian and 63 patients (64 %) presented psychological implication by the disease to necessitate clinical support. 42 patients (43%) were referred by team members. 13 patients (13%) presented to our center with suspect eosinophilic esophagitis. For these patients, ab initio evaluated with multidisciplinary approach, mean time to diagnosis was 2.25 months. Diagnostic delay reported in literature was 3 years.

Conclusion

Multidisciplinary team is needed to manage patients with eosinophilic esophagitis because its several associated diseases. In fact, most of our patients presented allergic, nutritional, and psychological disturbs. This approach assures more appropriate medical management through shared decision making. Almost half of patients was referred by team members. Thank to awareness of each physician of the team and his early referral, we assisted in a reduction of diagnostic delay in our center compared to data reported in literature.

References

Lenti MV, Savarino E, Mauro A, Penagini R, Racca F, Ghisa M, Laserra G, Merli S, Arsiè E, Longoni V, de Bortoli N, Sostilio A, Marabotto E, Ziola S, Vanoli A, Zingone F, Barberio B, Tolone S, Docimo L, Pellegatta G, Paoletti G, Ribolsi M, Repici A, Klersy C, Di Sabatino A. Diagnostic delay and misdiagnosis in eosinophilic oesophagitis. Dig Liver Dis. 2021 Dec;53(12):1632-1639. doi: 10.1016/j.dld.2021.05.017. Epub 2021 Jun 8. PMID: 34116974
Sauer BG, West A, McGowan EC. Multidisciplinary Eosinophilic Esophagitis Care: A Model for Comprehensive Patient-Centered Care Through Shared Decision Making Between Gastroenterology, Allergy, and Nutrition. Clin Gastroenterol Hepatol. 2021 Nov;19(11):2226-2229. doi: 10.1016/j.cgh.2021.07.025. Epub 2021 Jul 16. PMID: 34280551.
Murray FR, Kreienbuehl AS, Greuter T, Nennstiel S, Safroneeva E, Saner C, Schindler V, Schlag C, Schoepfer AM, Schreiner P, Straumann A, Biedermann L. Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis. Am J Gastroenterol. 2022 Nov 1;117(11):1772-1779. doi: 10.14309/ajg.0000000000001950. Epub 2022 Aug 12. PMID: 35971224.

Introduction

Endoscopic ultrasound-guided gallbladder drainage is usually reserved for high surgical risk patients. The procedure was usually performed under deep sedation to ensure the best tolerability for the patient and facilitate the endoscopist’s performance.
However, many of them showed a high-risk even for deep sedation.

Aims & Methods

Our aim was to evaluate the safety and efficacy of EUS-GBD under conscious sedation (CS).
All consecutive EUS-GBD under CS performed in our hospital were prospectively enrolled from January 2020 to December 2022.
Patient characteristics, type and dosage of anesthetic drug administered (Fentanyl (FNT), Pethidine (PTD) or Benzodiazepine (BZD)), size of lumen-apposing-metal-stent (LAMS), gallbladder (GB) access, technical success, clinical success, early and late adverse events (AEs) rate were evaluated. Safety was defined as AEs occurrence. The efficacy of EUS-GBD was expressed as technical and clinical success. We defined as “conscious sedation” a drug-induced depression of consciousness during which patients respond to verbal commands or react to touch. Breathing remains intact and no support is needed.

Results

A total of 49 patients (41.7% male, mean age 82,9±10 years-old) underwent EUS-GBD under in our Unit. Among all the 49 EUS-GBD in CS, 47 (95.9%) were indicated as treatment for acute cholecystitis in high-surgical-risk patients and 2 (4.1%) as rescue-strategy after ERCP fail.
In 45 (91.8%) EUS-GBD a 10x10mm LAMS was deployed, in 3 (6.2%) procedures a 15x10mm and in 1 (2%) an 8x8mm LAMS. GB was accessed from the duodenum in 68.8% of cases.
A combination of PTD+BZD was administered in 29 (59.2%) EUS-GBD, while 18 (36.7%) procedures were performed under FNT+BZD. Only 2 (4.1%) EUS-GBD were performed only under BZD.
Mean FNT, PTD, BZD dose were 50(±11.5) mcg, 38.4(±25.6) mg and 4(±1.5) mg, respectively.
Technical success of EUS-GBD under CS was 97.9%. In one procedure the distal flange of the LAMS did not open due to LAMS malfunction. The clinical success of EUS-GBD under CS was 97.9% since in one procedure there was not a decrease of inflammatory, cytolysis and cholestasis indices. Only in 1 (2%) EUS-GBD an early AE was reported. No late AEs were described.
The statistical analysis showed that the administration of a combination of fentanyl and benzodiazepine or a combination of pethidine and benzodiazepines or the administration of only benzodiazepines affected neither technical nor clinical success, nor AEs rate (Table 1).

Conclusion

EUS-GBD under CS was a safe procedure with a low AEs rate.
The administration of FNT+BZD, PTD+BZD or BZD alone did not affect procedure outcome.

Introduction

Pancreatic duct (PD) stones frequently occur in chronic calcifying pancreatitis (CCP) and are a main factor contributing to pain onset and exacerbation as well as impaired quality of life (QOL). In these patients endoscopic intervention with removal of obstructing pancreatic duct (PD) calculi and regaining pancreatic duct drainage should be performed. In this regard, digital single operator video pancreatoscopy (d-SOVP) is still under investigation for the treatment of PD stones but seems to be an emerging alternative to standard endoscopic procedures with reported success rates between 43%-100%, based on small retrospective studies. However, while reported short term success rates seem very promising, there is still poor evidence for long-term clinical success and benefit for patients` quality of life.

Aims & Methods

Aims: To investigate the role of d-SOVP guided PD-stone lithotripsy in patients with CCP on clinical success and QOL in a long-term follow-up (FU).
Methods: Patients with CCP undergoing d-SOVP (SpyGlass DS) guided lithotripsy of PD stones with initial technical and clinical success were recruited in this retrospective analysis. Persistence of technical success (ductal clearance) and clinical success (defined as pain reduction >50 % in numerical rating scale (NRS)) as well as postinterventional QOL were evaluated by database analysis and a systematic questionnaire (based on SF-12) regarding pain intensity and incidence, painkiller intake and impact on QOL every 6 months obtained in the respective outpatient clinic. Data are presented as mean±SD.

Results

A total of 32 patients was evaluated during long-term FU of 40.8±8.3 months (range 32 – 57 months). 81% of patients (26/32) reported a significant and lasting decrease in pain and symptom burden with mean decrease of NRS from 6.1±0.55 (preinterventionally) to 1.6±0.35 at last reported visit of FU, p<0.01. In 4 patients (12.5%) subsequent pancreatic duct stenting was required due to persistent PD strictures, no recurrent intraductal stones were observed. 3 patients (9.4%) reported persistent pain, with 2 of these being eligible for partial pancreatectomy. QOL criteria significantly improved in 81% of patients defined by major improvements of their general health status and everyday life performance. Two patients were lost to follow-up, 3 patients (9.4%) died during follow up.

Conclusion

D-SOVP guided lithotripsy is safe and effective, achieving high rates of initial technical and clinical success rates as defined by complete ductal clearance and QOL. Beneficial effects on symptom control and QOL persist in the majority of CCP patients after approximately 41 months of FU. Therefore, we suggest d-SOVP to become the intervention of choice in these complex patients. Nevertheless, further prospective trials are warranted to prove these results.

Disclosure

Mark Ellrichmann, Horst Neuhaus, Torsten Beyna and Christian Gerges received lecture from Boston Scientific.

Introduction

Infection is the main cause of decompensation in liver cirrhosis (LC) and contributes to high mortality. Infection by multidrug-resistant microorganisms (MDRO) is becoming increasingly prevalent, and there is evidence that it reduces survival in LC.

Aims & Methods

A 6-year retrospective analysis was carried out on a cohort of patients with LC admitted due to infection between October 2017 and March 2018. MDRO was defined as resistance to at least 3 antibiotic classes. The survival time in weeks from the date of MDRO isolation or date of hospitalization to the date of death was evaluated. SPSS was used to reproduce Kaplan-Meier (KM) survival curves.

Results

31 patients were included, 17 of whom had MDRO isolation vs. 14 without MDRO isolation (N-MDRO) during the 2017-2018 period. After the analysis period, 30 patients had died. A lower survival rate was observed in patients with MDRO isolation, with a mean survival rate of 37.9 weeks vs. 61.5 weeks for N-MDRO, although without statistical significance (p=0.7). From the subgroup analyses carried out, there was also a statistically non-significant lower average survival in the MDRO group: analyzing patients without a diagnosis of hepatocellular carcinoma (23 patients), there was an average survival of 47.9 weeks in the MDRO (12 patients) vs 75.7 weeks in the N-MDRO group (p=0.74); and in the subgroup with Child Pugh <C (12 patients), there was an average survival of 29.6 weeks in the MDRO (9 patients) vs 110.6 weeks in the N-MDRO group (p=0.18).

Conclusion

The results of this cohort, although not statistically significant, suggest that MDRO infection has an impact on the decreased survival of patients with LC, particularly in patients who would expect a longer survival.

References

Kaplan Meier curves of survival will be presented.